Signaling and Caveolin
A separate part of our work focuses on signaling proteins and receptors that bind to the caveolin scaffolding domain (CSD domain) in caveolin-3. This includes the insulin receptor and endothelial nitric oxides synthase (eNOS). For both proteins we can demonstrate that the activity and localization depends on the presence of caveolin-3 at the plasma membrane. This work has implications for vascular disease and for diabetes, two of the most common co-morbidities of obesity.
Figure 2: Palmitate induces translocation of cellular eNOS in HL-1 cardiomyocytes concomitant with the loss of caveolin-3. Cells treated with control conditions show localization of eNOS around the cell periphery (first row), while treatment with palmitate (0.4 mM) causes movement to the cell’s interior (second row). In addition, cells were treated with an inhibitor of the de novo ceramide synthesis pathway, myriocin (5 µM), which can prevent eNOS translocation during palmitate exposure (two bottom rows). Green = eNOS, Red = lipid, Blue = DNA, Yellow = areas of eNOS/lipid colocalization.
In our future work, we want to investigate how the lipid-induced loss of caveolin proteins can be prevented and what a potential pharmacological treatment to replace caveolin-3 in the heart may entail.